Clonal analysis of metachronous double biliary tract cancers.

The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and ß-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence-free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5-year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Comparison of physicians' and dentists' incident reports in open data from the Japan Council for Quality Health Care: a mixed-method study.

BACKGROUND: Patient safety is associated with patient outcomes. However, there is insufficient evidence of patient safety in the dental field. This study aimed to compare incidents reported by dentists and physicians, compare the type of errors made by them, and identify how dentists prevent dental errors. METHODS: A mixed-methods study was conducted using open data from the Japan Council for Quality Health Care database. A total of 6071 incident reports submitted for the period 2016-2020 were analyzed; the number of dentists' incident reports was 144, and the number of physicians' incident reports was 5927. RESULTS: The percentage of dental intern reporters was higher than that of medical intern reporters (dentists: n = 12, 8.3%; physicians: n = 180, 3.0%; p = 0.002). The percentage of reports by dentists was greater than that by physicians: wrong part of body treated (dentists: n = 26, 18.1%; physicians: n = 120, 2.0%; p < 0.001), leaving foreign matter in the body (dentists: n = 15, 10.4%; physicians: n = 182, 3.1%; p < 0.001), and accidental ingestion (dentists: n = 8, 5.6%; physicians: n = 8, 0.1%; p < 0.001), and aspiration of foreign body (dentists: n = 5, 3.4%; physicians: n = 33, 0.6%; p = 0.002). The percentage of each type of prevention method utilized was as follows: software 27.8% (n = 292), hardware (e.g., developing a new system) 2.1% (n = 22), environment (e.g., coordinating the activities of staff) 4.2% (n = 44), liveware (e.g., reviewing procedure, double checking, evaluating judgement calls made) 51.6% (n = 542), and liveware-liveware (e.g., developing adequate treatment plans, conducting appropriate postoperative evaluations, selecting appropriate equipment and adequately trained medical staff) 14.3% (n = 150). CONCLUSION: Hardware and software and environment components accounted for a small percentage of the errors made, while the components of liveware and liveware-liveware errors were larger. Human error cannot be prevented by individual efforts alone; thus, a systematic and holistic approach needs to be developed by the medical community.

Crystal structures of hydroxymethylbilane synthase complexed with a substrate analog: a single substrate-binding site for four consecutive condensation steps.

Hydroxymethylbilane synthase (HMBS), which is involved in the heme biosynthesis pathway, has a dipyrromethane cofactor and combines four porphobilinogen (PBG) molecules to form a linear tetrapyrrole, hydroxymethylbilane. Enzyme kinetic study of human HMBS using a PBG-derivative, 2-iodoporphobilinogen (2-I-PBG), exhibited noncompetitive inhibition with the inhibition constant being 5.4 ± 0.3 µM. To elucidate the reaction mechanism of HMBS in detail, crystal structure analysis of 2-I-PBG-bound holo-HMBS and its reaction intermediate possessing two PBG molecules (ES2), and inhibitor-free ES2 was performed at 2.40, 2.31, and 1.79 Šresolution, respectively. Their overall structures are similar to that of inhibitor-free holo-HMBS, and the differences are limited near the active site. In both 2-I-PBG-bound structures, 2-I-PBG is located near the terminus of the cofactor or the tetrapyrrole chain. The propionate group of 2-I-PBG interacts with the side chain of Arg173, and its acetate group is associated with the side chains of Arg26 and Ser28. Furthermore, the aminomethyl group and pyrrole nitrogen of 2-I-PBG form hydrogen bonds with the side chains of Gln34 and Asp99, respectively. These amino acid residues form a single substrate-binding site, where each of the four PBG molecules covalently binds to the cofactor (or oligopyrrole chain) consecutively, ultimately forming a hexapyrrole chain. Molecular dynamics simulation of the ES2 intermediate suggested that the thermal fluctuation of the lid and cofactor-binding loops causes substrate recruitment and oligopyrrole chain shift needed for consecutive condensation. Finally, the hexapyrrole chain is hydrolyzed self-catalytically to produce hydroxymethylbilane.

[A Case of Resected Pancreatic Adenosquamous Carcinoma with Early Hepatic Metastatic Recurrence].

A 73-year-old man was presented with epigastric pain and indicated high CA19-9 levels, and computed tomography detected a tumor in the uncinate process of the pancreas infiltrated duodenum and superior mesenteric artery. The patient was diagnosed with borderline resectable pancreatic carcinoma and received neoadjuvant chemotherapy with gemcitabine and S-1. During neoadjuvant chemotherapy, the patient also received radiotherapy to control duodenal bleeding. After neoadjuvant chemotherapy, stable disease(SD)was proven on the Response Evaluation Criteria in Solid Tumors(RECIST), and subtotal stomach-preserving pancreaticoduodenectomy was performed. The pathological findings showed pancreatic adenosquamous carcinoma. After 7 days postoperatively, hepatic metastasis was detected, and after 78 days postoperatively, the patient died.

[A Case of Scirrhous Gastric Cancer Not Diagnosed by Endoscopy but by Staging Laparoscopy].

A 71-year-old female was referred to our hospital for abdominal distention and anorexia. Gastrointestinal endoscopy revealed wall thickening of the entire circumference. Abdominal CT scan showed diffuse thickening of the stomach, but there was no obvious metastasis. Scirrhous gastric cancer was strongly suspected, but endoscopic biopsies could not demonstrate malignant features. Staging laparoscopy was performed. There was a small amount of ascites and numerous peritoneal dissemination. She was diagnosed with gastric cancer pStage Ⅳ(pT4a, NX, H0, M1, P1, CY1)without HER2 positivity. We experienced a case of scirrhous gastric cancer in which staging laparoscopy was useful for histological diagnosis and staging.

The product of trunk muscle area and density on the CT image is a good indicator of energy expenditure in patients with or at risk for COPD.

BACKGROUND: Physical inactivity due to cachexia and muscle wasting is well recognized as a sign of poor prognosis in chronic obstructive pulmonary disease (COPD). However, there have been no reports on the relationship between trunk muscle measurements and energy expenditure parameters, such as the total energy expenditure (TEE) and physical activity level (PAL), in COPD. In this study, we investigated the associations of computed tomography (CT)-derived muscle area and density measurements with clinical parameters, including TEE and PAL, in patients with or at risk for COPD, and examined whether these muscle measurements serve as an indicator of TEE and PAL. METHODS: The study population consisted of 36 male patients with (n = 28, stage 1-4) and at risk for (n = 8) COPD aged over 50 years. TEE was measured by the doubly labeled water method, and PAL was calculated as the TEE/basal metabolic rate estimated by the indirect method. The cross-sectional areas and densities of the pectoralis muscles, rectus abdominis muscles, and erector spinae muscles were measured. We evaluated the relationship between these muscle measurements and clinical outcomes, including body composition, lung function, muscle strength, TEE, and PAL. RESULTS: All the muscle areas were significantly associated with TEE, severity of emphysema, and body composition indices such as body mass index, fat-free mass, and trunk muscle mass. All trunk muscle densities were correlated with PAL. The product of the rectus abdominis muscle area and density showed the highest association with TEE (r = 0.732) and PAL (r = 0.578). Several trunk muscle measurements showed significant correlations with maximal inspiratory and expiratory pressures, indicating their roles in respiration. CONCLUSIONS: CT-derived measurements for trunk muscles are helpful in evaluating physical status and function in patients with or at risk for COPD. Particularly, trunk muscle evaluation may be a useful marker reflecting TEE and PAL.

[A Case of HER2 Positive Gastric Cancer That Was Highly Responsive to Fifth-Line Chemotherapy with Trastuzumab].

A 76-year-old male underwent distal gastrectomy for gastric cancer and pathological findings showed Stage Ⅳ(T4a, N3a, M1, H0, P0, CY1)with HER2 positivity. He received chemotherapy with S-1 and oxaliplatin(SOX)plus trastuzumab and no disease progression was shown. However, because of Grade 3 adverse skin effects to S-1, he could not continue with the regimen. He switched to a regimen of ramucirumab plus paclitaxel, followed by nivolumab, and later irinotecan. However, the disease progressed and multiple lung metastases as well as a left adrenal metastasis appeared. Fifth-line chemotherapy with trastuzumab was administered. After 4 courses, the lung metastases reduced and the left adrenal metastasis shrank from 46 mm to 33 mm. These results were consistent with a partial response on the Response Evaluation Criteria in Solid Tumors. In addition, CEA and CA19-9 also decreased significantly. Unfortunately, after 10 courses, the patient's disease progressed.

[Mucinous Cystadenocarcinoma with a Sarcomatous Component Arising from the Sigmoid Mesocolon-A Case Report].

A 53‒year‒old female was referred to our hospital for abdominal pain. A cystic tumor evolving since 12 years, which was suspected of being a lymphocyst, was detected in her left lower abdomen. Computed tomography(CT)revealed the cystic tumor with enhanced 80 mm enlarged regions. Regarding the laboratory data, inflammatory parameters and tumor markers such as CA19‒9, CEA, and CA125 were elevated. Mucinous cystadenocarcinoma was highly suspected and a surgery was performed. Laparotomy showed that the tumor was located in the sigmoid mesocolon and there were multiple peritoneal disseminations. The tumor could not be separated from the sigmoid colon; therefore, tumor resection with partial sigmoidectomy was performed. The resected specimens showed mucus and solid lesions in the cystic tumor. The pathological findings revealed that the cystic tumor from the sigmoid mesocolon was a mucinous cystadenocarcinoma with large spindle‒ shaped atypical cells, which were considered to have undergone sarcomatous changes. No cases of mucinous cystadenocarcinoma with sarcoma arising from the sigmoid mesocolon have been previously reported. The prognosis of mucinous cystic neoplasm with sarcoma is suspected to be very poor, and the accumulation of such cases could help in improving their treatment.

[Two Cases of Locally Advanced Colorectal Cancer Involving Pathological Complete Response after Chemotherapy].

We report 2 cases of locally advanced colorectal cancer in which complete response(CR)was achieved after chemotherapy. Case 1 involved a 71-year-old male diagnosed with rectal cancer invading the bladder. Chemotherapy with SOX plus bevacizumab and IRIS plus bevacizumab was administered for rectal cancer. Post-chemotherapy, the disease showed clinical CR(cCR)according to the Response Evaluation Criteria in Solid Tumors(RECIST). A laparoscopic abdominoperineal resection was then performed, with pathological findings showing no viable cancer cells. Eleven months postoperatively, the patient remains alive without disease recurrence. Case 2 involved a 54-year-old female diagnosed with a peritoneal abscess resulting from perforated sigmoid colon cancer. She received chemotherapy with SOX plus bevacizumab. Post-chemotherapy, the disease showed cCR according to the RECIST. A sigmoidectomy was performed, with pathological findings showing no viable cancer cells. Ten months postoperatively, the patient remains alive without disease recurrence. We believe that neoadjuvant chemotherapy is a feasible treatment option for locally advanced colorectal cancer.

[Two Cases of Resectable Liver Metastasis from Colorectal Cancer with Pathological Complete Response after Neoadjuvant Chemotherapy].

A 57-year-old male, who had received a laparoscopic low anterior resection for rectal cancer 12 months ago, was diagnosed a resectable liver metastasis from rectal cancer by computed tomography(CT). Neoadjuvant chemotherapy with mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab was performed for liver metastasis. After neoadjuvant chemotherapy, partial response(PR)was proved on the Response Evaluation Criteria in Solid Tumors(RECIST)and partial resection of the liver was conducted. Pathological findings showed no viable cancer cells. He is alive without recurrence 5 years after the surgery. A 70-year-old female, who had received a laparoscopic high anterior resection for rectal cancer 17 months ago, was diagnosed a resectable liver metastasis from rectal cancer by CT. SOX plus bevacizumab was performed for liver metastasis. After neoadjuvant chemotherapy, PR was proved on the RECIST and right hepatic lobectomy was performed. Pathological findings showed no viable cancer cells and she is alive without recurrence 4 years after the surgery. We expected neoadjuvant chemotherapy for resectable liver metastasis might be an option of treatment.

Combination of longitudinal pancreaticojejunostomy with coring-out of the pancreatic head (Frey procedure) and distal pancreatectomy for chronic pancreatitis.

PURPOSE: The Frey procedure is an effective surgery for chronic pancreatitis (CP) patients who have pancreatic head lesions with dilation of the main pancreatic duct. However, pancreatic tail lesions can cause relapsing pancreatitis after the procedure. Therefore, additional distal pancreatectomy (DP) might complement the therapeutic effect of the Frey procedure in controlling inflammation of the pancreatic tail. The Frey procedure with DP (Frey + DP) is indicated for inflammatory lesions in the pancreatic head and tail. In this study, we assessed the usefulness of Frey + DP using the retrospective clinical data of our cases. METHODS: The clinical outcomes were compared between CP patients who underwent the Frey procedure (N = 44) and Frey + DP (N = 13) from January 2005 to April 2016. RESULTS: Frey + DP showed similarly good therapeutic effects to the Frey procedure with regard to the postoperative stay, morbidity, mortality, pain relief and nutrition, although the Frey + DP had a longer operative time, more bleeding and higher incidence of diabetes mellitus than the Frey procedure because of the additional DP. One patient in the Frey group received additional DP because of recurrent pain due to the tail lesion. CONCLUSION: Frey + DP can be a promising treatment for CP patients with pancreatic head and tail lesions.

Frey's procedure for chronic pancreatitis improves the nutritional status of these patients.

PURPOSE: The aim of surgical intervention for chronic pancreatitis (CP) is to relieve symptoms and improve quality of life. However, the precise effect of surgery on the nutritional status of CP patients, which is often impaired by exocrine and endocrine pancreatic dysfunction, has not been elucidated. We conducted this study to evaluate whether Frey's procedure improves the nutritional status of CP patients. METHODS: The nutritional status of 35 patients who underwent Frey's procedure for CP at our institute between April 2005 and December 2014, was assessed by the controlling nutritional status (CONUT) scoring before and 1 year after the surgery, and compared with that of seven CP patients who underwent pancreatoduodenectomy. The occurrence of postoperative hepatic steatosis was also monitored. RESULTS: The nutritional status improved after Frey's procedure, but not after pancreatoduodenectomy. The median postoperative CONUT score after Frey's procedure was significantly lower than the preoperative score (1.0 ± 0.5 vs. 4.0 ± 2.5; p < 0.001). CONCLUSION: Frey's procedure is superior to pancreatoduodenectomy for improving the nutritional status of CP patients.

Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells.

Basophils and mast cells play critical roles in host defense against pathogens and allergic disorders. However, the molecular mechanism by which these cells are generated is not completely understood. Here we demonstrate that interferon regulatory factor-8 (IRF8), a transcription factor essential for the development of several myeloid lineages, also regulates basophil and mast cell development. Irf8(-/-) mice displayed a severe reduction in basophil counts, which was accounted for by the absence of pre-basophil and mast cell progenitors (pre-BMPs). Although Irf8(-/-) mice retained peripheral tissue mast cells, remaining progenitors from Irf8(-/-) mice including granulocyte progenitors (GPs) were unable to efficiently generate either basophils or mast cells, indicating that IRF8 also contributes to the development of mast cells. IRF8 appeared to function at the GP stage, because IRF8 was expressed in GPs, but not in basophils, mast cells, and basophil/mast cell-restricted progenitor cells. Furthermore, we demonstrate that GATA2, a transcription factor known to promote basophil and mast cell differentiation, acts downstream of IRF8. These results shed light on the pathways and mechanism underlying the development of basophils and mast cells.

Structural basis for the electron transfer from an open form of NADPH-cytochrome P450 oxidoreductase to heme oxygenase.

NADPH-cytochrome P450 oxidoreductase (CPR) supplies electrons to various heme proteins including heme oxygenase (HO), which is a key enzyme for heme degradation. Electrons from NADPH flow first to flavin adenine dinucleotide, then to flavin mononucleotide (FMN), and finally to heme in the redox partner. For electron transfer from CPR to its redox partner, the ''closed-open transition'' of CPR is indispensable. Here, we demonstrate that a hinge-shortened CPR variant, which favors an open conformation, makes a stable complex with heme-HO-1 and can support the HO reaction, although its efficiency is extremely limited. Furthermore, we determined the crystal structure of the CPR variant in complex with heme-HO-1 at 4.3-Å resolution. The crystal structure of a complex of CPR and its redox partner was previously unidentified. The distance between heme and FMN in this complex (6 Å) implies direct electron transfer from FMN to heme.

Effective treatment for infantile hemangioma with long-pulsed dye laser with oral propranolol medication: a preliminary report.

PURPOSE: To investigate the efficacy of our treatment of infantile hemangioma (IH)s retrospectively presenting as disfiguring or functionally threatening lesions. MATERIALS AND METHODS: 25 infants with IH treated with long-pulsed dye laser or laser with or without propranolol. Tumor fading after treatment was evaluated using both color and size rating scales, before, during and after treatment. RESULTS: 6 infants were treated by laser, 11, oral propranolol and 8 using both treatments. Each treatment was effective for most IH with a median treatment duration of 7.7 months for laser, and 13.3 months for the latter two. Combination therapy was the most effective in both color-fading and size reduction by the 3rd month. Laser alone was most effective in color-fading with almost complete disappearance of most tumors. Oral propranolol to the three site-specific IHs was effective with disappearance of tumors. There were no apparent side effects related to laser treatment, but one infant suffered from allergy and another from bronchial asthma due to propranolol medication. CONCLUSIONS: Most IHs discolored and regressed considerably with these treatments, including complete disappearance of the three functionally threatening lesions. This combined approach is quite useful for accelerating tumor regression.

Relation between amount of bile ducts in portal canal and outcomes in biliary atresia.

BACKGROUND: There is no good prognostic indicator for biliary atresia (BA). We reviewed liver biopsies taken during the initial procedure to find a prognostic marker. METHODS: Thirty-two BA cases underwent Kasai operation from 1976 to 2009. We compared two groups at 1, 3, and 9 years. Group A required liver transplantation or died. Group B survived with their native liver. Biopsies were analyzed for liver fibrosis, portal-central vein bridging (P-C bridging), ductal plate malformation (DPM) and the number of the bile ducts in portal canal/measured surface area of the portal canal (BDP ratio). Statistical comparisons of the multiple data were evaluated by Mann-Whitney U test, Student's t test and Pearson's Chi-square test. Regression analysis with P < 0.05 was considered significant. RESULTS: BDP ratios (/mm(2)) were 2.4 ± 1.5 in Group A1 (n = 9) vs 4.6 ± 2.4 in Group B1 (n = 23) (P = 0.01); 2.6 ± 1.4 in Group A3 (n = 14) vs 5.1 ± 2.5 in Group B3 (n = 18) (P < 0.01), 3.0 ± 2.2 in Group A9 (n = 15) vs 4.9 ± 2.5 in Group B9 (n = 15) (P < 0.05). There was no significant difference in any other finding. CONCLUSION: The BDP ratio is a sound prognostic indicator in BA.

Essential role of the IRF8-KLF4 transcription factor cascade in murine monocyte differentiation.

Monocytes regulate host defenses, inflammation, and tissue homeostasis. The transcription factor interferon regulatory factor-8 (IRF8) stimulates monocyte/macrophage differentiation, yet genome-wide understanding of the differentiation program initiated by IRF8 is lacking. By combining chromatin immunoprecipitation sequencing with gene expression profiling, we show that during IRF8-dependent monocyte differentiation, IRF8 binding occurs at both promoter-proximal and promotor-distal regions together with the transcription factor PU.1 and is associated with gene induction. Many of the promoter-distal IRF8 binding sites show an increase in histone H3 lysine 4 monomethylation, a signature for enhancers. However, about half the IRF8-induced genes were not bound by IRF8, suggesting the involvement of downstream transcription factors. Analysis of DNA motifs in cis-regulatory elements of these indirect IRF8 target genes predicted that Krüppel-like factor-4 (KLF4)-essential for Ly6C(+) monocyte development-is one such factor. Indeed, monocyte development in Irf8(-/-) mice is as defective as that in Klf4(-/-) chimeric mice. Moreover, Irf8(-/-) monocyte-dendritic cell progenitors do not express Klf4 messenger RNA. Introduction of KLF4 into an Irf8(-/-) myeloid progenitor cell line induced a subset of IRF8 target genes and caused partial monocyte differentiation. Taken together, our present results uncover genome-wide behavior of IRF8 and identify an IRF8-KLF4 axis that operates during monocyte differentiation.

The current strategy for urachal remnants.

BACKGROUND: Optimal therapy for urachal remnant (UR) in children is controversial. Nonoperative management for symptomatic UR is an alternative. Many papers support the laparoscopic approach but the indication for this is unclear. We review our experience to determine the optimal management of UR. MATERIALS AND METHODS: A retrospective chart review of patients from 1990 to 2013 with UR was performed. Patients were analyzed according to age, gender, initial symptoms, type of UR, treatment, and outcome. RESULTS: We identified 27 patients (M:F = 17:10). A urachal sinus was found in 16 cases (59%), a urachal cyst in 5 (18%) and a urachal duct in 6 (22%). Eleven (A) were under 1 year, with 16 over 1 year (B). In Group A, the commonest symptom was umbilical granulation (n = 6, 54%). Group B was dominated by abdominal pain (n = 12, 75%). Six cases in Group A needed operation for repeated infections. In 5 cases, the UR disappeared. In Group B, 2 cases were followed conservatively. The others required surgery. From 2009, we utilized a laparoscopic approach (LA, n = 7) rather than the classical umbilical approach (UA, n = 13). The operation time was not significantly different (LA = 124 min: UA = 110 min, P > 0.05). There was a tendency for shorter hospital stay following LA (LA = 7.5 days: UA = 10.9 days). Complete resection was always possible using UA in Group A but a more caudal incision (mean 3.6 cm) was required in group B. LA enabled confirmation of the complete resection with three 5 mm ports in Group B. There were no operative complications after LA against two wound infections, one of which suffered a disruption, after UA. CONCLUSION: Conservative follow-up is recommended for UR under 1-year old except when there are repeated infections. The umbilical approach is enough for infants. Laparoscopic surgery is recommended in older children.

Adenocarcinoma arising in small sessile serrated adenoma/polyp (SSA/P) of the colon: clinicopathological study of eight lesions.

We reviewed the clinicopathological findings of eight cases of sessile serrated adenoma/polyps (SSA/Ps) with carcinoma, the largest diameter of which was 10 mm or less. All lesions were polyps located in the right side of the colon. Four lesions showed submucosal invasion and one lesion invaded the proper muscle layer. The depth of invasion, however, did not seem to be related to the carcinoma area size. Most carcinomas were well to moderately differentiated tubular adenocarcinomas focally showing some serrated appearances, and the predominant component of one carcinoma was a poorly differentiated medullary growth with inflammatory stroma. Rapid progression to invasive carcinoma from SSA/P was suggested for the carcinoma with proper muscle invasion whereas one submucosally invasive carcinoma was considered to progress over 7 years. Immunohistochemically, it was suggested that with or without hMLH1 protein loss, alterations of p53 and/or Wnt signaling pathway can be involved in the cancerization through SSA/Ps. The carcinomas irregularly imitated the mucin expression of the SSA/Ps (positive for MUC5AC and MUC2, and MUC6 expression in crypt bases), which was lost with progression of the carcinomas. Analyses of small SSA/P lesions with cancerization would facilitate the understanding of the mode of progression of SSA/Ps and their early detection.

[A case of a patient with gastric cancer and peritoneal dissemination who survived for more than 10 years after successful treatment with S-1].

A 50-year-old female patient underwent distal gastrectomy and intraperitoneal CDDP administration for advanced gastric cancer accompanied by severe peritoneal dissemination. She valued her quality of life and chose an oral anticancer drug, S-1, as a postoperative chemotherapy agent. S-1 was administered at a dose of 100mg/body/day for 4 weeks, followed by a 2- week rest. There were no adverse events due to S-1 and no exacerbation of peritoneal dissemination in the 5 years following surgery. The S-1 administration schedule was then changed to alternate-day administration. Eight years after the surgery, the patient discontinued S-1 treatment and has since survived for 11 years with no obvious cancer recurrence.